Nicola Longo

Validation of the 2009 TNM Version in a Large Multi-Institutional Cohort of Patients Treated for Renal Cell Carcinoma: Are Further Improvements Needed?

BACKGROUND A new edition of the TNM was recently released that includes modifications for the staging system of kidney cancers. Specifically, T2 cancers were subclassified into T2a and T2b (< or =10 cm vs >10 cm), tumors with renal vein involvement or perinephric fat involvement were classified as T3a cancers, and those with adrenal involvement were classified as T4 cancers. OBJECTIVE Our aim was to validate the recently released edition of the TNM staging system for primary tumor classification in kidney cancer. DESIGN, SETTING, AND PARTICIPANTS Our multicenter retrospective study consisted of 5339 patients treated in 16 academic Italian centers. INTERVENTION Patients underwent either radical or partial nephrectomy. MEASUREMENTS Univariable and multivariable Cox regression models addressed cancer-specific survival (CSS) after surgery. RESULTS AND LIMITATIONS In the study, 1897 patients (35.5%) were classified as pT1a, 1453 (27%) as pT1b, 437 (8%) as pT2a, 153 (3%) as pT2b, 1059 (20%) as pT3a, 117 (2%) as pT3b, 26 (0.5%) as pT3c, and 197 (4%) as pT4. At a median follow-up of 42 mo, 786 (15%) had died of disease. In univariable analysis, patients with pT2b and pT3a tumors had similar CSS, as did patients with pT3c and pT4 tumors. Moreover, both pT3a and pT3b stages included patients with heterogeneous outcomes. In multivariable analysis, the novel classification of the primary tumor was a powerful independent predictor of CSS (p for trend <0.0001). However, the substratification of pT1 tumors did not retain an independent predictive role. The major limitations of the study are retrospective design, lack of central pathologic review, and the small number of patients included in some substages. CONCLUSIONS The recently released seventh edition of the primary tumor staging system for kidney tumors is a powerful predictor of CSS. However, some of the substages identified by the classification have overlapping prognoses, and other substages include patients with heterogeneous outcomes. The few modifications included in this edition may have not resolved the most critical issues in the previous version.

Simple Enucleation is Equivalent to Traditional Partial Nephrectomy for Renal Cell Carcinoma: Results of a Nonrandomized, Retrospective, Comparative Study

PURPOSE The excision of the renal tumor with a substantial margin of healthy parenchyma is considered the gold standard technique for partial nephrectomy. However, simple enucleation showed excellent results in some retrospective series. We compared the oncologic outcomes after standard partial nephrectomy and simple enucleation. MATERIALS AND METHODS We retrospectively analyzed 982 patients who underwent standard partial nephrectomy and 537 who had simple enucleation for localized renal cell carcinoma at 16 academic centers between 1997 and 2007. Local recurrence, cancer specific survival and progression-free survival were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions and differences were assessed with the log rank statistic. Univariable and multivariable Cox regression models addressed progression-free survival and cancer specific survival. RESULTS Median followup of the patients undergoing traditional partial nephrectomy and simple enucleation was 51 ± 37.8 and 54.4 ± 36 months, respectively (p = 0.08). The 5 and 10-year progression-free survival estimates were 88.9 and 82% after standard partial nephrectomy, and 91.4% and 90.8% after simple enucleation (p = 0.09). The 5 and 10-year cancer specific survival estimates were 93.9% and 91.6% after standard partial nephrectomy, and 94.3% and 93.2% after simple enucleation (p = 0.94). On multivariable analysis the adopted nephron sparing surgery technique was not an independent predictor of progression-free survival (HR 0.8, p = 0.55) and cancer specific survival (HR 0.7, p = 0.53) when adjusted for the effect of the other covariates. CONCLUSIONS To our knowledge this is the first multicenter, comparative study showing oncologic equivalence of standard partial nephrectomy and simple enucleation.

Elective partial nephrectomy is equivalent to radical nephrectomy in patients with clinical T1 renal cell carcinoma: results of a retrospective, comparative, multi‐institutional study

Study Type – Therapy (cohort)

Features associated with recurrence beyond 5 years after nephrectomy and nephron-sparing surgery for renal cell carcinoma: Development and internal validation of a risk model (PRELANE score) to predict late recurrence based on a large multicenter database (CORONA/SATURN Project)

BACKGROUND Approximately 10-20% of recurrences in patients treated with nephrectomy for renal cell carcinoma (RCC) develop beyond 5 yr after surgery (late recurrence). OBJECTIVE To determine features associated with late recurrence. DESIGN, SETTING, AND PARTICIPANTS A total of 5009 patients from a multicenter database comprising 13 107 RCC patients treated surgically had a minimum recurrence-free survival of 60 mo (median follow-up [FU]: 105 mo [range: 78-135]); at last FU, 4699 were disease free (median FU: 103 mo [range: 78-134]), and 310 patients (6.2%) experienced disease recurrence (median FU: 120 mo [range: 93-149]). INTERVENTIONS Patients underwent radical nephrectomy or nephron-sparing surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable regression analyses identified features associated with late recurrence. Cox regression analyses evaluated the association of features with cancer-specific mortality (CSM). RESULTS AND LIMITATIONS Lymphovascular invasion (LVI) (odds ratio [OR]: 3.07; p<0.001), Fuhrman grade 3-4 (OR: 1.60; p=0.001), and pT stage >pT1 (OR: 2.28; p<0.001) were significantly associated with late recurrence. Based on accordant regression coefficients, these parameters were weighted with point values (LVI: 2 points; Fuhrman grade 3-4: 1 point, pT stage >1: 2 points), and a risk score was developed for the prediction of late recurrences. The calculated values (0 points: late recurrence risk 3.1%; 1-3 points: 8.4%; 4-5 points: 22.1%) resulted in a good-, intermediate- and poor-prognosis group (area under the curve value for the model: 70%; 95% confidence interval, 67-73). Multivariable Cox regression analysis showed LVI (HR: 2.75; p<0.001), pT stage (HR: 1.24; p<0.001), Fuhrman grade (HR: 2.40; p<0.001), age (HR: 1.01; p<0.001), and gender (HR: 0.71; p=0.027) to influence CSM significantly. Limitations are based on the multicenter and retrospective study design. CONCLUSIONS LVI, Fuhrman grade 3/4, and a tumor stage >pT1 are independent predictors of late recurrence after at least 5 yr from surgery in patients with RCC. We developed a risk score that allows for prognostic stratification and individualized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design.

Time to recurrence is a significant predictor of cancer‐specific survival after recurrence in patients with recurrent renal cell carcinoma – results from a comprehensive multi‐centre database (CORONA/SATURN‐Project)

To assess the prognostic impact of time to recurrence (TTR) on cancer‐specific survival (CSS) after recurrence in patients with renal cell carcinoma (RCC) undergoing radical nephrectomy or nephron‐sparing surgery. To analyse differences in clinical and histopathological criteria between patients with early and late recurrence.

A New Biopsy Technique to Investigate Peyronie’s Disease Associated Histologic Alterations: Results with Two Different Forms of Therapy

OBJECTIVES Peyronies disease is the most frequent cause of penile curvature and occurs particularly in middle-age patients. The best technique for penile biopsy, in the evaluation of albuginea and cavernous tissue, has not been delineated yet. We present a new technique of penile biopsy, useful in the study of Peyronies plaque, fibrosis and erectile dysfunction or any other pathological condition of the penis requiring a biopsy. METHODS A treatment group (A) of 380 patients underwent Extra Shock Waves Treatment (ESWT) three times a week for 20 minutes, followed by a complete cycle of 12 injections of verapamil (10mg), every two weeks for six months. A control group (B) of 92 patients underwent verapamil injections alone. Three months after the end of the treatment, each patient underwent penile biopsy performed with Acu-Punch (Acuderm Inc.), a biopsy-punch armed with a well-sharpened rotating cylindrical blade, first used by dermatologists for cutaneous lesions. RESULTS A reduction of the plaque volume was found in 260/380 patients (68.4%) of group A and in 28/92 (30.4%) of group B; painful erection weaned off in 312/340 patients of group A (91.7%) and in 36/82 patients (43.9%) of group B. In all 472 patients an excellent specimen was obtained and both the tunica albuginea and the cavernous tissue were easily identified. In the 260 cases, in which the Extra Shock Waves Treatment was successful, scanning and transmission electron microscopy demonstrated a reduction in packing and clumping of the collagen fibers. CONCLUSIONS This new technique of penile biopsy with Acu-Punch can replace surgical biopsies when a surgical operation is not indicated. Such a low-invasive technique could be performed in all cases of Peyronies disease and allows a more extensive use of microscopic analysis in the study of Peyronies disease.

α1-Blockers Improve Benign Prostatic Obstruction in Men with Lower Urinary Tract Symptoms: A Systematic Review and Meta-analysis of Urodynamic Studies☆

CONTEXT The urodynamic outcomes for α1-blockers (ABs) treatment in patients with lower urinary tract symptoms related to benign prostatic enlargement (LUTS/BPE) is a matter of debate. OBJECTIVE To perform a systematic review and meta-analysis of studies evaluating the ABs urodynamic outcomes in patients with LUTS/BPE. The primary endpoint was variation in bladder outlet obstruction index (BOOI). Secondary endpoints were the maximum urinary flow rate (Qmax) and detrusor pressure at Qmax (PdetQmax). A meta-analysis of placebo-controlled randomized clinical trials (RCTs) was performed to compare ABs with placebo. EVIDENCE ACQUISITION A systematic review of PubMed/Medline, ISI Web of Knowledge, and Scopus databases was performed in May 2015. Seventeen studies were selected for inclusion. EVIDENCE SYNTHESIS The overall pooled data showed a mean BOOI change of -14.19 (p<0.0001), a mean PdetQmax change of -11. 39cm H2O (p<0.0001), and a mean Qmax improvement of 2.27ml/s (p<0.0001). Subgroup analysis showed a mean BOOI change of -14.88 (p=0.01) for alfuzosin, -19.41 (p=0.01) for doxazosin, -16.47 (p<0.0001) for naftopidil, -30.45 (p<0.0001) for silodosin, -14.27 (p=0.002) for tamsulosin, and -6.69 (p=0.005) for terazosin. Subanalysis of RCTs containing a placebo arm showed a significant improvement in BOOI in patients undergoing ABs treatment. Meta-regression revealed a significant positive association between the percentage of patients with obstruction at baseline and the improvement in BOOI after treatment with ABs. CONCLUSION ABs improve BOOI in patients with LUTS/BPE mainly by reducing PdetQmax, and this effect is higher in patients presenting with urodynamic obstruction at baseline. The free Qmax variation underestimates the real effect of ABs on benign prostatic obstruction. PATIENT SUMMARY Results of this meta-analysis suggest that α1-blockers objectively improve urinary voiding function in patients with benign prostatic obstruction.

Prognostic factors in a large multi-institutional series of papillary renal cell carcinoma

Study Type – Prognosis cohort series (multi‐centre)

Corrigendum to “Validation of the 2009 TNM Version in a Large Multi-Institutional Cohort of Patients Treated for Renal Cell Carcinoma: Are Further Improvements Needed?” [Eur Urol 2010;58:588–95]

Giacomo Novara , Vincenzo Ficarra *, Alessandro Antonelli , Walter Artibani , Roberto Bertini , Marco Carini , Sergio Cosciani Cunico , Ciro Imbimbo , Nicola Longo , Guido Martignoni , Giuseppe Martorana , Andrea Minervini , Vincenzo Mirone , Francesco Montorsi , Riccardo Schiavina , Claudio Simeone , Sergio Serni , Alchiede Simonato , Salvatore Siracusano , Alessandro Volpe , Giorgio Carmignani h

TriMatch comparison of the efficacy of FloSeal versus TachoSil versus no hemostatic agents for partial nephrectomy: Results from a large multicenter dataset

To evaluate the efficacy of hemostatic agents, TachoSil and FloSeal, during partial nephrectomy using a large multicenter dataset.